The interactions of different strains of Acholeplasma laidlawii and the complement proteins are being investigated. One strain, comr-328, and a strain derived from it, comr-328-2 are resistant to lysis by the complement cascade as measured by hexokinase release. There is a significant difference in glycolipid and lipoglycan neutral sugar content. Compared to the wild type strain, comr-328 appears to synthesize a large excess of lipoglycan, suggesting that the neutral sugar content plays a role in complement interaction with mycoplasmas. Ten strains of A. laidlawii including the complement resistant comr-328 and comr-328-2 were exposed to C4 deficient guinea pig serum containing 125I-labeled C3. Cleavage of C3 to form C3b was found to occur in every case. Therefore all of the strains appear to be capable of activating the alternative complement pathway. When sheep erythrocytes are mixed with either comr-328 or wild type, followed by the addition of C4 deficient guinea pig serum, lysis of the erythrocytes occurs. The red blood cell lysis could be due to the activation of complement by the bacteria which may be adhering to the erythrocytes, rather than the adherence of complement-coated mycoplasmas to the erythrocytes. This "bystander lysis" effect will be investigated further in order to elucidate the mechanism by which it occurs and to determine whether it relates to the hemolytic anemia which in certain instances is associated with human mycoplasma pneumonia.